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Aims: People in remote areas may have more difficulty accessing healthcare following myocardial infarction (MI) than people in metropolitan areas. We determined whether remoteness was associated with initial and 12-month use of secondary prevention medications following MI in Victoria, Australia., Methods and Results: We included all people alive at least 90 days after discharge following MI between July 2012 and June 2017 in Victoria, Australia (n = 41 925). We investigated dispensing of P2Y12 inhibitors (P2Y12i), statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs), and beta-blockers within 90 days after discharge. We estimated 12-month medication use using proportion of days covered (PDC). Remoteness was determined using the Accessibility/Remoteness Index of Australia (ARIA). Data were analysed using adjusted parametric regression models stratified by ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). There were 10 819 STEMI admissions and 31 106 NSTEMI admissions. Following adjustment across NSTEMI and STEMI, there were no medication classes dispensed in the 90-day post-discharge that differed in a clinically significant way from the least remote (ARIA = 0) to the most remote (ARIA = 4.8) areas. The largest difference for NSTEMI was ACEI/ARB, with 71% (95% confidence interval 70-72%) vs. 80% (76-83%). For STEMI, it was statins with 89% (88-90%) vs. 95% (91-97%). Predicted PDC for STEMI and NSTEMI was not clinically significant across remoteness, with the largest difference in NSTEMI being P2Y12i with 48% (47-50%) vs. 55% (51-59%), and in STEMI, it was ACEI/ARB with 68% (67-69%) vs. 76% (70-80%)., Conclusion: Remoteness does not appear to be a clinically significant driver for medication use following MI. Possible differences in cardiovascular outcomes in metropolitan and non-metropolitan areas are not likely to be explained by access to secondary prevention medications., Competing Interests: Conflict of interest: A.C.L., Z.A., D.P., and J.I.M. have no conflicts to declare relevant to this publication. J.I. has received grants from the NHMRC, National Breast Cancer Foundation, Dementia Australia Research Foundation, AstraZeneca. and Amgen. J.S.B. is supported by a National Health and Medical Research Council (NHMRC) Boosting Dementia Research Leadership Fellowship and has received grant funding or consulting funds from the NHMRC, Medical Research Future Fund, Victorian Government Department of Health, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Programme, Amgen, and several aged care provider organizations unrelated to this work. All grants and consulting funds were paid to the employing institution., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: We aimed to assess the cost effectiveness of four different lipid-lowering strategies for primary prevention of coronary heart disease initiated at ages 30, 40, 50, and 60 years from the UK National Health Service perspective., Methods: We developed a microsimulation model comparing the initiation of a lipid-lowering strategy to current standard of care (control). We included 458,692 participants of the UK Biobank study. The four lipid-lowering strategies were: (1) low/moderate-intensity statins; (2) high-intensity statins; (3) low/moderate-intensity statins and ezetimibe; and (4) inclisiran. The main outcome was the incremental cost-effectiveness ratio for each lipid-lowering strategy compared to the control, with 3.5% annual discounting using 2021 GBP (£); incremental cost-effectiveness ratios were compared to the UK willingness-to-pay threshold of £20,000-£30,000 per quality-adjusted life-year., Results: The most effective intervention, low/moderate-intensity statins and ezetimibe, was projected to lead to a gain in quality-adjusted life-years of 0.067 per person initiated at 30 and 0.026 at age 60 years. Initiating therapy at 40 years of age was the most cost effective for all lipid-lowering strategies, with incremental cost-effectiveness ratios of £2553 (95% uncertainty interval: 1270, 3969), £4511 (3138, 6401), £11,107 (8655, 14,508), and £1,406,296 (1,121,775, 1,796,281) per quality-adjusted life-year gained for strategies 1-4, respectively. Incremental cost-effectiveness ratios were lower for male individuals (vs female individuals) and for people with higher (vs lower) low-density lipoprotein-cholesterol. For example, low/moderate-intensity statin use initiated from age 40 years had an incremental cost-effectiveness ratio of £5891 (3822, 9348), £2174 (772, 4216), and was dominant (i.e. cost saving; -2,760, 350) in female individuals with a low-density lipoprotein-cholesterol of ≥ 3.0, ≥ 4.0 and ≥ 5.0 mmol/L, respectively. Inclisiran was not cost effective in any sub-group at its current price., Conclusions: Low-density lipoprotein-cholesterol lowering from early ages is a more cost-effective strategy than late intervention and cost effectiveness increased with the increasing lifetime risk of coronary heart disease., (© 2023. Crown.)

Competing Interests: Conflict of interest: ZA and JIM declare no conflict of interest. DL declares grants from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Pfizer and Sanofi, and past participation in advisory boards and/or receipt of honoraria from Abbvie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Edwards Lifesciences, Novartis, Pfizer, Sanofi and Shire, outside the submitted work. SJN has received research support and/or honoraria for Amgen, AstraZeneca, Eli Lilly, Esperion, Novartis, Merck, Pfizer, Iowa and Sanofi-Regeneron.

Although studies of nonstatin lipid-lowering therapies have demonstrated cardiovascular benefits; whether these benefits provide good value has not been evaluated in type 2 diabetes mellitus patients. A systematic review was performed to include studies on the cost-effectiveness of non-statin lipid-lowering therapies in type 2 diabetes mellitus patients with/without cardiovascular disease. Thirteen studies were included; ezetimibe (n = 8), proprotein convertase subtilisin/kexin type 9 inhibitors (n = 4), fenofibrate (n = 2), nicotinic acid (n = 1), extended-release niacin/laropiprant (n = 1), and icosapent ethyl (n = 1). Six studies considered ezetimibe + statin to be a cost-effective compared to statins monotherapy, three studies suggested that proprotein convertase subtilisin/kexin type 9inhibitors + statins were not cost-effective compared to statin + ezetimibe. Fenofibrate was a cost-effective either as monotherapy or combined with a statin compared to statin or fenofibrate monotherapy. Nicotinic acid and proprotein convertase subtilisin/kexin type 9 compared to statin monotherapy were also cost-effective. Icosapent ethyl was cost-effective compared to standard care but not using the wholesale acquisition cost., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in statin-treated patients remains suboptimal. We quantified the health economic impact of delayed lipid-lowering intensification from an Australian healthcare and societal perspective., Methods: A lifetime Markov cohort model (n = 1000) estimating the impact on coronary heart disease (CHD) of intensifying lipid-lowering treatment in statin-treated patients with uncontrolled LDL-C, at moderate to high risk of CHD with no delay or after a 5-year delay, compared with standard of care (no intensification), starting at age 40 years. Intensification was tested with high-intensity statins or statins + ezetimibe. LDL-C levels were extracted from a primary care cohort. CHD risk was estimated using the pooled cohort equation. The effect of cumulative exposure to LDL-C on CHD risk was derived from Mendelian randomization data. Outcomes included CHD events, quality-adjusted life-years (QALYs), healthcare and productivity costs, and incremental cost-effectiveness ratios (ICERs). All outcomes were discounted annually by 5%., Results: Over the lifetime horizon, compared with standard of care, achieving LDL-C control with no delay with high-intensity statins prevented 29 CHD events and yielded 30 extra QALYs (ICERs AU$13 205/QALY) versus 22 CHD events and 16 QALYs (ICER AU$20 270/QALY) with a 5-year delay. For statins + ezetimibe, no delay prevented 53 CHD events and gave 45 extra QALYs (ICER AU$37 271/QALY) versus 40 CHD events and 29 QALYs (ICER of AU$44 218/QALY) after a 5-year delay., Conclusions: Delaying attainment of LDL-C goals translates into lost therapeutic benefit and a waste of resources. Urgent policies are needed to improve LDL-C goal attainment in statin-treated patients., (Copyright © 2022. Published by Elsevier Inc.)

Background: Statins are widely prescribed for the primary and secondary prevention of cardiovascular disease (CVD), but their effectiveness is dependent on the level of adherence and persistence., Objectives: This study aimed to explore the patterns of switching, adherence and persistence among the Australian general population with newly dispensed statins., Methods: A retrospective cohort study was conducted using a random sample of data from the Australian national prescription claims data. Switching, adherence to and persistence with statins were assessed for people starting statins from 1 January 2015 to 31 December 2019. Switching was defined as either switching to another intensity of statin, to another statin or to a non-statin agent. Non-persistence to treatment was defined as discontinuation (i.e. ≥90 days with no statin) of coverage. Adherence was measured using proportion of days covered (PDC), and patients with PDC < 0.80 were considered non-adherent. Cox proportional hazard models were used to compare discontinuation, switching and reinitiation between different statins., Results: A cohort of 141,062 people dispensed statins and followed over a median duration of 2.5 years were included. Of the cohort, 29.3% switched statin intensity, 28.4% switched statin type, 3.7% switched to ezetimibe and in 2.7%, ezetimibe was added as combination therapy during the study period. Overall, 58.8% discontinued statins based on the 90-day gap criteria, of whom 55.2% restarted. The proportion of people non-adherent was 24.0% at 6 months to 49.0% at 5 years. People on low and moderate intensity statins were more likely to discontinue compared to those on high-intensity statins (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.31), (HR 1.28, 95%CI 1.14-1.42), respectively. Compared to maintaining same statin type and intensity, switching statins, which includes up-titration (HR 0.77, 95%CI 0.70 to 0.86) was associated with less likelihood of discontinuation after reinitiation., Conclusions: Long-term persistence and adherence to statins remains generally poor among Australians, which limits the effectiveness of these medicines and the consequent health impact they may provide for individuals (and by extension, the population impact when poor persistence and adherence is considered in the statin-taking population). Switching between statins is prevalent in one third of statin users, although any clinical benefit of the observed switching trend is unknown. This, combined with the high volume of statin prescriptions, highlights the need for better strategies to address poor persistence and adherence., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Little is known about the attainment of low-density lipoprotein cholesterol (LDL-C) targets in patients treated with statins in Australian primary healthcare setting that are at increased risk of cardiovascular disease. A retrospective cohort study was conducted using data from electronic medical records of patients treated by general practitioners across Australia. LDL-C target attainment was defined as LDL-C levels ≤ 2 mmol/L for all risk groups, in line with Australian guidelines. Multivariable logistic regression was used to identify the factors associated with LDL-C target attainment. Overall, 61,407 patients were included in the analysis. The mean age was 65 years (± standard deviation [SD] 12.1); 52.0% were males.. Overall, the median LDL-C level was 2.3 mmol/L (IQR = 1.8 - 2.8) and 36.0% of the study population met therapeutic targets. Increased likelihood to achieve LDL-C targets was observed in patients diagnosed with type 2 diabetes (OR 2.07, 95% CI 1.92 - 2.24), stroke (OR = 1.58, 95% CI 1.39 - 1.79, P < 0.001) or chronic heart disease (OR = 1.67, 95% CI 1.55 - 1.81, P < 0.001). Patients diagnosed with dyslipidemia (OR = 0.59, 95% CI 0.55 - 0.64, P < 0.001), hypertension (OR = 0.91, 95% CI 0.83 - 1.00, P < 0.05) and current smokers (OR = 0.71, 95% CI 0.71 - 1.00, P < 0.05), were less likely to attain LDL-C targets, regardless of the type, intensity and length of use of the prescribed statin. Longer duration and higher intensity statin were associated with more patients achieving targeted LDL-C goal, however nearly two thirds of Australians still failed to achieve targeted outcome even after 24 months of statin therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in real-world settings among patients receiving combination lipid-lowering therapy (LLT, statins plus non-statins) is not well characterised., Objective: To evaluate LDL-C levels and LDL-C goal attainment in patients treated with combination LLT in real-world primary care settings., Methods: A retrospective cohort study of patients treated with combination LLT. Data were drawn from general practitioner electronic medical records across Australia from 2013 to 2019. The on-treatment goal for LDL-C was < 2 mmol/L (77 mg/dL), as per Australian guidelines., Results: The cohort analysed included 9,173 individuals treated with combination LLT. The mean age was 65.8 years (standard deviation [SD] 11.5), 60.1% were males, and 56.7% had at least one cardiovascular risk factor. The median on-treatment LDL-C was 2.1 mmol/L (IQR 1.6-2.8), and overall 45.4% of the cohort met LDL-C goals, with individuals on fixed-dose combination of statins plus ezetimibe having the highest rates of achievement (49.8%). In multivariable logistic regression analyses, factors associated with LDL-C goal achievement were male sex (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.3-1.6, p < 0.001), aged >80 years (OR 4.2, 95% CI 1.5 - 6.6, p = 0.006), and a history of T2DM (OR 1.7; 95% CI 1.5-1.9, p < 0.001) or coronary heart disease (OR 1.4, 95% CI 1.2 - 1.6, p < 0.001)., Conclusions: More than half of Australians on combination LLT did not achieve LDL-C goals. Urgent measures are needed to address this gap in clinical practice to minimise negative health outcomes., Competing Interests: Declaration of Competing Interest CM, SVT, MP, ST, DA and ZA have nothing to declare; SL and DT are employed by Amgen Australia Pty Ltd or other Amgen subsidiaries; GS is employed by IQVIA; EZ declares grants from Amgen, AstraZeneca, Pfizer and Shire, outside the submitted work; DL declares grants from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Pfizer and Sanofi, and past participation in advisory boards and/or receipt of honoraria from Abbvie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Edwards Lifesciences, Novartis, Pfizer, Sanofi and Shire, outside the submitted work., (Copyright © 2022. Published by Elsevier Inc.)

Lipid-lowering medications comprise standard of care in the prevention of cardiovascular disease. This study examined the trends in the utilization of statin and non-statin medications in the Australian general population between 2013 and 2019. Pharmacoepidemiological analyses were performed using pharmacy dispensing data from Australian Pharmaceutical Benefits Scheme. One-year prevalence and incidence of statin and non-statin prescribing patterns were reported, and relative variations in prescribing examined via Poisson regression modelling. The one-year prevalence of statins' prescriptions decreased between 2013-2019 by 5.5% (from 25.0%-19.5%). Females were less likely than males to be prescribed statins (rate ratio [RR]=0.90, 95% confidence interval [CI] 0.89-0.91). The one-year prevalence of ezetimibe alone, and in combination with statins, increased consistently from 2013-2019 from 1.5%-3.6% (P<0.01) and 0.1%-1.1% (P<0.01), respectively. The prevalence was higher among those aged 61-80 years (RR=1.20, 95%CI 1.10-1.21) and those aged older than 80 years (RR=1.34, 95%CI 1.22-1.47), when compared to people aged <60 years. The incidence of ezetimibe prescriptions was highest in people aged 61-80 years (RR=1.36, 95%CI 1.31-1.41) compared to those aged <60 years. The one-year prevalence of proprotein convertase subtilisin/kexin type 9 inhibitor prescriptions was highest among those aged 46-60 years (RR=1.24, 95%CI 0.97-4.97) compared to people aged <46 and >60 years. Females were less likely than males to be prescribed a proprotein convertase subtilisin/kexin type 9 inhibitor (RR=0.87, 95%CI 0.75-0.98). Statins remain the most prevalent lipid-lowering medication prescribed in Australia. The prescribing of non-statin medications remains low, but is increasing., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to estimate the cost-effectiveness, from the perspective of the Australian public healthcare system, of icosapent ethyl in combination with statin therapy compared with statin alone for the prevention of cardiovascular disease., Methods and Results: A Markov model populated with data from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial was designed to predict the effectiveness and costs of icosapent ethyl in combination with statins compared with statins alone over a 20-year time horizon. Data inputs for costs and utilities were sourced from published sources. The annual costs of icosapent ethyl were assumed to be AUD1637 (USD2907) per person. All future costs and outcomes were discounted annually by 5%. The main outcome of interest was incremental cost-effectiveness ratios in terms of cost per quality adjusted life year (QALY) gained and per year of life saved (YoLS). Over a 20-year time horizon, compared with statin alone, icosapent ethyl in combination with statin was estimated to cost an additional AUD$13,022 per person, but led to 0.338 YoLS and 0.289 QALYs gained (all discounted). These equated to incremental cost-effectiveness ratios of AUD45,036 per QALY gained and AUD38,480 per YoLS. Sub-analyses for primary and secondary prevention were AUD96,136 and AUD35,935 per QALY gained, respectively. The results were sensitive to time-horizon, age related trends and the acquisition price of icosapent ethyl., Conclusion: Compared with statin alone, icosapent ethyl in combination with statin therapy is likely to be cost-effective in the prevention of cardiovascular disease assuming a willingness-to-pay threshold of AUD50,000 per QALY gained, especially in the secondary preventive setting., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Using non-statin lipid-modifying agents in combination with statin therapy provides additional benefits for cardiovascular disease (CVD) risk reduction, but their value for money has only been evaluated in high-income countries (HICs). Furthermore, studies mainly derive effectiveness data from a single trial or older meta-analyses., Objectives: Our study used data from the most recent network meta-analysis (NMA) and local parameters to assess the cost effectiveness of non-statin agents in statin-treated patients with a history of CVD., Methods: A published Markov model was adopted to investigate lifetime outcomes: (1) number of recurrent CVD events prevented, (2) quality-adjusted life-years (QALYs) gained, (3) costs and (4) incremental cost-effectiveness ratios (ICERs) of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and ezetimibe added to statin therapy. Event rates and effectiveness inputs were obtained from the NMA. Cost and utility data were gathered from published studies conducted in Thailand. A series of sensitivity analyses were performed., Results: Patients receiving PCSK9i and ezetimibe experienced fewer recurrent CVD events (number needed to treat [NNT] 17 and 30) and more QALYs (0.168 and 0.096 QALYs gained per person). However, under the societal perspective and at current acquisition costs in 2018, ICERs of both agents were $US1,223,995 and 27,361 per QALY gained, respectively. Based on threshold analyses, the costs need to be reduced by 97 and 85%, respectively, for PCSK9i and ezetimibe to be cost-effective., Conclusions: Despite the proven effectiveness of PCSK9i and ezetimibe, the costs of these agents need to reduce to a much greater extent than in HICs to be cost-effective in Thailand.

Background: Individuals with metabolic syndrome (MetS) are at increased risk of cardiovascular disease (CVD), often requiring combination drug therapy for control of risk factors and subsequent risk reduction. This study aims to compare the long-term effectiveness and cost effectiveness of the polypill (a multi-component tablet), and its components (alone or in combination), in a MetS population., Methods and Results: A Markov state transition model, using individual subject data from the Australian Diabetes, Obesity and Lifestyle study, was constructed to simulate the effects of the treatment versus no treatment on CVD events, and costs over 10 years. In 1,991 individuals classified as MetS and free of existing diabetes mellitus or CVD, treatment with the polypill (or its components) was effective at reducing cardiovascular events [statin: 171, aspirin (actetylsalicylic acid): 201, antihypertensive: 186 per 1,000 individuals]. The more drug therapies employed the greater the reduction, with the polypill reducing up to 351 cardiovascular events per 10,000 individuals. Cost-effectiveness analyses were sensitive to drug treatment costs and effectiveness of treatment. At a cost of AUD$42 per person per annum, aspirin was considered cost saving. All other treatment strategies, including the polypill, were not cost effective., Conclusion: The polypill is likely to be effective in the reduction of cardiovascular events in a MetS population. It is, however, not cost effective. Nevertheless, in a high-risk population, among whom combination therapy is often prescribed, the polypill is likely to be more cost effective than antihypertensive therapy alone or dual therapy with a statin and antihypertensive combination.

Background: Although few cardiovascular registries report the costs of illness or cost-effectiveness of health interventions, such information is critical to inform the effective and cost-effective management of cardiovascular disease, particularly if drawn from population-based registries, which more accurately reflect clinical practice and follow up patients for much longer than clinical trials., Objective: The goal of this study was to estimate the cost-effectiveness of closing the statin "treatment gap" in the secondary prevention of coronary artery disease (CAD) in Australia., Methods: A decision analysis Markov model was developed with yearly cycles and the health states of alive or dead. Using data from the Australian Reduction of Atherothrombosis for Continued Health Registry, the model compared current statin coverage (82%) in the secondary prevention of CAD (the current group) with a hypothetical situation of 100% coverage (the improved group). The 18% gap was filled with use of generic statins. Data from a recent meta-analysis were used to estimate the benefits of statin use in terms of reducing recurrent cardiovascular events and death. Government reimbursement data from 2011 were used to calculate direct health care costs. The cost of the intervention to improve statin coverage was assumed to be $250 per person. Years of life lived and costs were discounted at 5% annually. All values are given in Australian dollars., Results: Among the 2058 subjects in the current group, the model estimated that there would be 106 nonfatal myocardial infractions, 68 nonfatal strokes, and 275 deaths over 5 years. In the improved group, all of whom took statins, the corresponding numbers were 101, 65, and 259, equating to numbers needed to treat of 426, 639, and 127, respectively. Over the 5 years, there would be 0.018 life-years gained (discounted) at a net cost of $546 (discounted) per person. These equated to an incremental cost-effectiveness ratio of $29,717 per life-year gained., Conclusion: The results suggest that for patients with CAD, maximizing coverage with statins, in line with evidence-based recommendations, represents a cost-effective means of secondary prevention., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)